Injection of leptin into white adipose tissue (WAT) increased sympathetic outflow to the epididymal WAT (Niijima, 1998) and kidney (Tanida et al, 2000) in rats. The sensory and efferent sympathetic innervations of WAT were well documented (Bartness & Song, 2007). We recently found that the sympatho-excitatory reflex, adipose afferent reflex (AAR), was caused not only by leptin, but also by capsaicin, bradykinin or adenosine in WAT, and chemical lesion of paraventricular nucleus (PVN) neurons with kainic acid abolished the AAR induced by WAT injection of capsaicin in normal rats (Shi et al, 2012). More recently, we found that the AAR was enhanced in obesity and obesity-related hypertension rats, and the enhanced AAR contributes to sympathetic activation in obesity hypertension (Xiong et al. 2012). It is unknown whether ionotropic glutamate receptors including N-methyl-D-aspartate (NMDA) and non-N-methyl-D-aspartate (non-NMDA) receptors in the PVN are involved in mediating the AAR. Experiments were carried out in male Sprague-Dawley rats weighing between 300 and 400 g. Each rat was anesthetized by intraperitoneal injection of urethane (800 mg/kg) and α-chloralose (40 mg/kg). Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. AAR was evaluated by the the RSNA and MAP responses to the injections of capsaicin (1.0 nmol/μl) into four sites of the right inguinal WAT at a rate of 4.0 μl min-1 for 2 min for each site. Values are means ± SE, compared by ANOVA. Compared with the bilateral PVN microinjection of saline, either NMDA receptor (NMADR) antagonist AP5 (1, 3, 9 or 27 nmol) or non-NMDA receptor (non-NMDAR) antagonist CNQX (1, 3, 9 or 27 nmol) attenuated the AAR in a dose-related manner. AP5 plus CNQX completely abolished the AAR Compared with saline treated rats, the RSNA responses to capsaicin in AP5 (9 nmol), CNQX (9 nmol) and AP5 plus CNQX treated rats were 3.6±0.8, 5.9±1.4 and 0.2±1.1 % vs. 17.0±2.5 %, respectively (n=6 for each group, P<0.01); the RSNA responses to capsaicin in NR2A antagonist NVP-AAM077, NR2B antagonist CP-101,606 and NVP-AAM077 plus CP-101,606 treated rats were 10.0±2.2, 11.1±2.1 and 4.2±1.5 % vs. 17.0±2.5, respectively (n=6 for each group, P<0.05). The results indicate that both NMDAR and non-NMDAR in the PVN mediate the AAR. Both NR2A and NR2B subunits of NMDAR in the PVN are involved in the NMDAR-mediated AAR.